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bcl ‐2 enhancement of malignant transformation in mouse epidermal JB6 cells
Author(s) -
Amstad Paul A.,
Liu Hui,
Ichimiya Masato,
Chang Seung,
Berezesky Irene K.,
Trump Benjamin F.
Publication year - 1997
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/(sici)1098-2744(199710)20:2<231::aid-mc10>3.0.co;2-b
Subject(s) - transfection , biology , transactivation , carcinogenesis , microbiology and biotechnology , activator (genetics) , cell culture , transcription factor , cancer research , gene , biochemistry , genetics
Increased bcl‐2 expression is a common feature of many types of human malignancies, which implies that bcl‐2 plays an important role in tumorigenesis. To better understand the molecular mechanisms of bcl‐2 –induced oncogenesis, we examined the effects of bcl‐2 expression on transformation of mouse epidermal JB6 cells induced by the tumor promoter 12‐ O ‐tetradecanoylphorbol‐13‐acetate (TPA). Promotion‐sensitive JB6 clone41 cells were transfected with the bcl‐2 –containing expression vector pD 5 ‐neo/bcl‐2, and the soft agar growth of bcl‐2 –transfected cells and control cells were compared. bcl‐2 overexpression in JB6 clone41 cells caused a TPA‐induced soft‐agar growth fivefold greater than the growth of nontransfected or vector‐transfected (neo control) cells. bcl‐2 expression in the absence of TPA did not lead to colony formation in soft agar. Because the level of the transcription factor activator protein 1 (AP‐1) has been shown to be critical for the responsiveness of JB6 cells to TPA‐induced transformation, we compared c‐ jun and c‐ fos expression as well as the AP‐1–binding activity and the AP‐1–mediated transactivation of the reporter construct TRE‐CAT between bcl‐2 –expressing cells and control cells. When compared with control cells, bcl‐2 –transfected cells expressed significantly more c‐ fos but not c‐ jun after TPA treatment. Furthermore, the levels of AP‐1 and AP‐1–induced transactivation of TRE‐CAT were greater in bcl‐2 –transfected cells than in control cells after TPA treatment. These results showed that bcl‐2 cooperates with a tumor promoter such as TPA in the induction of malignant transformation in mouse epidermal cells and that bcl‐2 enhances soft‐agar growth by stimulating signaling pathways that led to increased AP‐1 expression. Mol. Carcinog. 20:231–239, 1997. © 1997 Wiley‐Liss, Inc.